Recent advances in basic and tumor immunology have led to an increased understanding of the factors influencing the host immune response to tumors. The application of this knowledge and data identifying tumor- specific antigens, to the design of tumor-specific vaccines, holds the promise of resulting in the successful immunization of patients with cancer, as well as patients at high risk for cancer recurrence. T cells are a critical component of antigen-specific immune responses, influencing antibody production, professional antigen-presenting cell (APCs) function and natural killer cell activity. The broad objective of this proposal is to augment the immune response to specific antigens using strategies aimed at enhancing the T cell response. Particular vectors used to deliver antigens for immune priming in vivo may alter antigen processing, leading to increased association with both MHC class I and II presentation to CD8+ and CD4+ T cells, respectively. By expressing antigen along with stimulatory molecules or cytokines, the nature of the T cell response may be favorably influenced. Using the HER2/neu proto-oncogene transgenic mouse model of breast cancer, and the product of HER2/neu as a tissue- specific antigen for targeting antitumor immune responses, multiple recombinant vaccinia constructs will be compared head-to-head to test recombinant vaccines for treating cancer. Recombinant vaccine strategies demonstrating immune priming will be tested together with strategies for providing co-stimulation and enhanced access to target antigens, for enhancing the magnitude a duration of the immunity generated.